The long-term objective of this research is to understand the role of prolactin and its receptors in prolactin-dependent mammary tumor growth. Mammary tumors have a selective advantage in their host because of their hypersensitivity to prolactin-induced growth. The mechanisms responsible for this well-known observation are unknown. We propose that this phenomenon is due to disruptions in the normal routes of intracellular prolactin and prolactin receptor trafficing and in the transcellular prolactin transport pathway which in normal differentiated mammary cells, delivers prolactin to milk. One expression of these defects is our observation that mammary tumors contain a unique class of intracellular "cryptic" receptors whose expression at the cells surface is triggered, in part, by depleting cells of energy. Using primary cultures of carcinogen-induced rat mammary tumors and short-term organ cultures of normal and neoplastic rat mammary tissue, we propose to: (1) characterize the subcellular compartments involved in intracellular movement of prolactin and its receptors in mammary tumors, (2) compare prolactin processing in tumors with that in normal mammary tissue during differentiation and determine the relationship of hormone and receptor compartmentalization and the appearance and loss of cryptic receptors during differentiation, and (3) explore the mechanism(s) responsible for unmasking cryptic receptors.